Schizophrenia Bulletin vol. 39 no. 6 pp.

13431351, 2013
doi:10.1093/schbul/sbs117
Advance Access publication October 6, 2012

Functional Connectivity Measures After Psilocybin Inform a Novel Hypothesis

ofEarly Psychosis

Robin L.Carhart-Harris*,1,2, RobertLeech3, DavidErritzoe1, Tim M.Williams2, James M.Stone1, JohnEvans4,

David J.Sharp3, AmandaFeilding5, Richard G.Wise4, and David J.Nutt1,2
Imperial College London, Centre for Neuropsychopharmacology, Division of Experimental Medicine, London, UK; 2University of
1

Bristol, Academic Unit of Psychiatry, Bristol, UK; 3Imperial College London, the Computational, Cognitive, and Clinical Neuroimaging
Laboratory, Division of Experimental Medicine, London, UK; 4Cardiff University Brain Research Imaging Centre, School of

Downloaded from http://schizophreniabulletin.oxfordjournals.org/ at Universite Laval on July 5, 2014

Psychology, Cardiff University, Cardiff, UK; 5The Beckley Foundation, Beckley Park, Oxford, UK
*To whom correspondence should be addressed; Imperial College London, Centre for Neuropsychopharmacology, Burlington Danes
Building, 160 Du Cane Rd, London, UK; e-mail: r.carhart-harris@imperial.ac.uk

Psilocybin is a classic psychedelic and a candidate drug Introduction

model of psychosis. This study measured the effects of
psilocybin on resting-state network and thalamocortical
functional connectivity (FC) using functional magnetic
resonance imaging (fMRI). Fifteen healthy volunteers
received intravenous infusions of psilocybin and placebo in
2 task-free resting-state scans. Primary analyses focused
on changes in FC between the default-mode- (DMN) and
task-positive network (TPN). Spontaneous activity in the
DMN is orthogonal to spontaneous activity in the TPN,
and it is well known that these networks support very differ-
ent functions (ie, the DMN supports introspection, whereas
the TPN supports externally focused attention). Here, inde-
pendent components and seed-based FC analyses revealed
increased DMN-TPN FC and so decreased DMN-TPN
orthogonality after psilocybin. Increased DMN-TPN FC
has been found in psychosis and meditatory states, which
share some phenomenological similarities with the psy-
chedelic state. Increased DMN-TPN FC has also been
observed in sedation, as has decreased thalamocortical FC,
but here we found preserved thalamocortical FC after psi-
locybin. Thus, we propose that thalamocortical FC may be
related to arousal, whereas DMN-TPN FC is related to the
separateness of internally and externally focused states.
We suggest that this orthogonality is compromised in early
psychosis, explaining similarities between its phenomenol-
ogy and that of the psychedelic state and supporting the
utility of psilocybin as a model of early psychosis.
Key words: serotonin/5-HT/resting-state networks/
default-mode network/psychedelics/consciousness/
psychosis/at-risk mental state
Background
Psilocybin is a tryptamine psychedelic and the prodrug
of the major psychoactive component of magic mush-
rooms, psilocin. Psilocybin and psilocin were first iso-
lated and synthesized by Albert Hofmann1 after which
they were used in psychotherapy before this was cur-
tailed by political pressure.2 Classic psychedelics like
psilocybin produce a range of subjective effects from
superficial perceptual changes to more profound exis-
tential-type experiences.3 Much has been written about
the phenomenology of the psychedelic state, but we
have only a limited understanding of how it is produced
in the brain.
Functional MRI Measures of Spontaneous Brain
Activity
There has been an increased interest in measures of
spontaneous brain activity in recent years.4 In humans,
fMRI measures of task-free- or resting-state functional
connectivity (FC) have become popular. Measures of
resting-state FC using independent components analysis
(ICA) have identified a number of spatiotemporally
coherent networks5 that closely resemble stimulus-evoked
activation maps.6 Of particular interest is the default-
mode network (DMN), a network of regions (including
the posterior cingulate cortex; medial prefrontal cortex,
mPFC; and lateral inferior parietal cortex) that show
greater activity during internally oriented cognition
than externally focused attention.7 The DMN receives

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1343
R. L.Carhart-Harris etal
more blood flow8 and consumes more energy7 than other
brain regions, has undergone significant evolutionary
expansion,9 and serves as an important convergence zone
or connector hub in the cortex.10 The DMN is activated
during high-level cognitions such as predicting the future11;
making personal, social, and moral judgments12,13; and
contemplating the past.14 These properties have led to
speculations that the DMN is the biological system upon
which our psychological notions of self15 or ego16 are
based.
Between-Network FC and Cognitive Function
The DMN is known to deactivate during cognitive tasks,
while a generic task-positive network (TPN) is activated;
and the TPN deactivates during introspection, while
the DMN becomes more active. Importantly, this com-
petitive relationship between DMN and TPN activity
may be preserved under task-free conditions,17 poten-
tially implying that DMN-TPN competition, or at least
orthogonality, is a fundamental property of global brain
function.18
Spontaneous fluctuations in resting-state network
(RSN) activity influence stimulus-evoked activity and
predict behavioral variability.19 Task performance is more
consistent or less variable if inverse coupling between the
DMN and TPN is greater.20 Moreover, increased sponta-
neous DMN activity has been associated with increased
mind wandering.21 Thus, a picture emerges of a funda-
mental orthogonality between the DMN and TPN, with
the DMN serving explorative inner thought, and the
TPN serving focused attention. Crucially, during nor-
mal waking consciousness, explorative inner thought and
focused attention do not occur simultaneously, presum-
ably because the systems that support these states are
kept apart. If, however, activity in the DMN and TPN
was to become less orthogonal, then this might cause a
confusion of states and a disturbance of cognition such
as is seen in early psychosis.
Pharmacological fMRI studies have discovered rela-
tionships between changes in DMN-TPN FC and changes
in subjective experience. For example, abstinent smokers
with improved cognition following nicotine replacement
therapy showed increased inverse coupling between the
DMN and TPN.22 Changes in DMN-TPN and thalamo-
cortical coupling have also been measured after propofol
infusion. Reduced conscious awareness correlated with
reduced inverse coupling between the DMN and TPN
and decreased thalamocortical FC.23
The present study sought to test the effect of psilocy-
bin on DMN-TPN and thalamocortical FC. We hypoth-
esized that thalamocortical FC would be preserved after
psilocybin but DMN-TPN FC would be increasedcon-
sistent with reduced orthogonality between these net-
works in the psychedelic state.
1344
Materials and Methods
Design
This was a within-subjects placebo-controlled study. The
study was approved by a local NHS Research Ethics
Committee and Research and Development department,
and conducted in accordance with Good Clinical Practice
guidelines. AHome Office Licence was obtained for stor-
age and handling of a Schedule 1 drug. The University of
Bristol sponsored the research.
Participants
This is a new analysis on a previously published data set.24
Fifteen healthy subjects took part: 13 males and 2 females
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(mean age=32, SD=8.9). Recruitment was via word of
mouth. All subjects were required to give informed con-
sent and undergo health screens prior to enrolment. Entry
criteria were the following: at least 21years of age, no per-
sonal or immediate family history of a major psychiatric
disorder, substance dependence, cardiovascular disease,
and no history of a significant adverse response to a hallu-
cinogenic drug. All of the subjects had used psilocybin at
least once before (mean number of uses per subject=16.4,
SD=27.2) but not within 6 weeks of the study.
AnatomicalScans
Imaging was performed on a 3T GE HDx system.
Anatomical scans were performed before each functional
scan. These were 3D fast spoiled gradient echo scans in an
axial orientation, with field of view=256 256 192 and
matrix=256 256 192 to yield 1-mm isotropic voxel res-
olution (repetition time/echo time [TR/TE]=7.9/3.0ms;
inversion time=450ms; flip angle=20).
Drug and Scanning Parameters
All subjects underwent two 12-min eyes-closed resting-
state blood oxygenlevel dependent (BOLD) fMRI scans
on 2 separate occasions at least 7 days apart: placebo
(10ml saline, 60-s intravenous injection) was given on 1
occasion and psilocybin (2mg dissolved in 10ml saline)
on the other. Seven of the subjects received psilocybin in
scan 1, and 8 received it in scan 2.Injections were given
manually by a study doctor situated within the scanning
suite. The 60-s infusions began exactly 6min after the
start of the 12-min scans. Subjective ratings were given
postscan using visual analog scales. The subjective effects
of psilocybin were felt almost immediately after injection
and were sustained for the duration of the scan.25
fMRI Data Acquisition
BOLD-weighted fMRI data were acquired using a gra-
dient echo planar imaging sequence, TR/TE 3000/35ms,

field-of-view=192mm, 64 64 acquisition matrix, par-
allel acceleration factor = 2, 90 flip angle. Fifty-three
oblique axial slices were acquired in an interleaved fash-
ion, each 3mm thick with zero slice gap (3 3 3mm decreased orthogonality between the DMN and TPNs
voxels).
Independent Components Analysis
All analyses were performed using the Functional
Magnetic Resonance Imaging of the Brain (FMRIB)
Software Library (FSL, www.fmrib.ox.ac.uk/fsl). FSLs
MELODIC was used to derive 20 spatiotemporally coher-
ent components from 30 concatenated data sets. Twenty
preinjection baseline components were derived so that
the effect of psilocybin on FC between these components
could then be examined. Thus, the data sets from which
the components were derived included the first 6min of
each subjects placebo and psilocybin resting-state scans
(ie, the 100 volumes that were acquired prior to the injec-
tion of saline or psilocybin). These data were motion cor-
rected using FSLs MCFLIRT function and a high-pass
filter of 100 s was applied. The 20 components were reg-
istered to the subjects T1-weighted high-resolution (1
1 1mm) anatomical scans that were themselves regis-
tered to the Montreal Neurological Institute standard
brain (1 1 1mm).
Between-Network FC UsingICA
Of the 20 components derived from the group ICA, 11
were identified as functionally meaningful RSNs;
explicitly, we excluded 9 components where the majority
of the voxels were in white matter, ventricular space, or
outside of the brain. Henceforth, we will refer to these
as noise components because their signal was most
likely nonneuronal. The remaining 11 RSNs included an
anteriorly loaded DMN (aDMN), a posteriorly loaded
DMN (pDMN), right- and left-lateralized frontoparietal
networks (rFPN & lFPN), an auditory network (AUD),
salience network (SAL), visual network, precuneus net-
work, dorsal attention network (DAN), cerebellar net-
work, and sensorimotor network. These 11 networks are
shown in figure1 with the aDMN in everyimage.
Time series for the last 100 volumes (postinjection) for
all 20 components were extracted using multiple regres-
sion. Our analyses focused on the relationship between the
DMN and other RSN in the psychedelic state. Thus, the
aDMN was chosen as the dependent variable in regression
analyses run in SPSS. One RSN at a time plus the 9 noise
components were entered as independent variables. The
noise components were included to remove nonneuronal
variance. This process was repeated for each of the RSNs,
with the aDMN as the dependent variable in every case.
The unstandardized regression coefficient for the RSN of
interest were plotted and compared across the 2 conditions
(psilocybin vs placebo) in paired t tests. All t tests were 2
Functional Connectivity Measures
tailed. Pearsons correlational analyses were used to test
for relationships between aDMN-RSN FC and subjec-
tive ratings. Based on their relevance to the hypothesis that
would predict experiences of disturbed ego boundaries
and cognition, we chose the following 5 questionnaire
items for correlational analyses: I felt a sense of merging
with my environment, I experienced a loss of separation
from my surroundings, my thinking was muddled, I
lost all sense of ego, and the item that required subjects
to rate the intensity of the drug effects. Results were cor-
rected for multiple comparisons (Bonferonni).
Between-Network FC Using Seed-BasedFC
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In addition to the ICA approach, we assessed DMN-TPN
FC using seed-based FC. The results of a ventromedial
PFC (vmPFC) seed-based resting-state FC analysis were
used to define the DMN (vmPFC-positive network) and
TPN (vmPFC-negative network).24 Activity in these net-
works is sometimes referred to as being anticorrelated,
but this can be misleading because anticorrelations can
be introduced by regressing out the global grey matter
signal.18 For this reason, we chose not to include global
grey matter regression in any of the analyses presented
in this article. The DMN and TPN (cluster threshold
Z > 2.3, P < .05 whole brain corrected) were converted
into spatial masks from which time series were extracted
for each functional scan. We also extracted times series
from white matter and cerebrospinal fluid (CSF) masks
to serve as nonneuronal noise regressors.
Linear regression was performed to calculate the FC
strengths between the DMN and TPN for all of the scan-
ning sessions. Times series were separated into the first 100
volumes (preinjection) and the last 100 volumes (postin-
jection), with the 40 volumes surrounding the injection
period excluded from the analysis. The DMN time series
served as the dependent variable and the TPN, white mat-
ter, and CSF time series, plus motion parameters served
as independent variables. The unstandardized regression
coefficients for the DMN vs TPN were compared before
vs after psilocybin injection, plus after placebo vs after
psilocybin injection, using t tests.
ThalamicFC
To test for an effect of psilocybin on FC between the thala-
mus and high-level cortical networks, a bilateral thalamic
mask was generated based on an anatomical template in
FSL. This mask was thresholded and transformed into sin-
gle-subject functional space, and time series were extracted
for each subject. Linear regression was used to measure
changes in thalamocortical connectivity after psilocybin.
The thalamic time series served as the dependent variable,
and the DMN and TPN time series served as independent
variables. Thalamus-DMN and thalamus-TPN FC were
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Fig.1. Default-mode network-resting-state network (DMN-RSN) connectivity after psilocybin vs after placebo. (A) anteriorly loaded
DMN (aDMN)-left frontoparietal network connectivity, (B) aDMN-right frontoparietal connectivity, (C) aDMN-dorsal attention
network connectivity, (D) aDMN-salience network connectivity, (E) aDMN-visual network connectivity, (F) aDMN-auditory network
connectivity, (G) aDMN-motor network connectivity, (H) aDMN-cerebellar network connectivity, (I) aDMN-precuneus network
connectivity, (J) aDMN-posterior DMN connectivity. Images show the aDMN in orange and the relevant RSN in blue with the adjacent
chart displaying the regression coefficient or functional connectivity (FC) strength after placebo (gray) and psilocybin (blue). The
betas on the y-axis refer to regression coefficients. Contrasts B, C, D and F were all statistically significant when corrected for multiple
comparisons (corrected =0.005).

1346

calculated in 2 separate regression analyses. As before,
white matter and CSF time series and motion variance
were entered as regressors of no interest. Again, global
grey matter signal regression was not included in this anal-
ysis. Regression coefficients for thalamus-DMN and thal-
amus-TPN FC were compared before and after psilocybin
and placebo, and after psilocybin vs after placebo.
Results
Subjective Effects
The subjective effects of psilocybin have been docu-
mented elsewhere.24,25 Briefly, the subjective effects of
2mg psilocybin given as an intravenous injection over 60 s
begin at the end of the injection period, reach a sustained
peak after 4min, and subside completely after 4560min.
Primary subjective effects include altered visual percep-
tion (eg, hallucinated motion and geometric patterns), an
altered sense of space and time, and vivified imagination.
ICA and Between-NetworkFC
Eleven RSNs were identified from the preinjection time
series. These RSNs are listed in the Materials and Methods
section and shown in figure1. Of these 11 networks, there
were 2 DMNs, an anteriorly loaded DMN (aDMN, fig-
ure1, orange in all images) with all of the major DMN
nodes present, and a posteriorly loaded DMN (pDMN,
blue in figure 1J). FC between the aDMN and each of
the 10 remaining networks was compared in turn. Charts
in figure1 show the strength of the FC between aDMN
and the other RSNs after placebo and after psilocybin.
Significant increases in FC between the aDMN and the
SAL were evident after psilocybin (P=.0002), as well as
the right frontoparietal network (P = .0003), the AUD
(P = .0006), and the DAN (P = .0009). There was also
a suggestion of decreased FC between the anterior and
posterior DMNs (P=.02), but this did not survive cor-
rection for multiple comparisons (=0.005, Bonferonni
corrected). An example of increased aDMN-SAL FC
after psilocybin is shown in Figuer2C.
Seed-Based FC and Between-NetworkFC
A vmPFC seed-based FC analysis24 was used to derive
DMN and TPN spatial masks (figure 3A, orange and
blue, respectively). Linear regression revealed signifi-
cantly increased FC between the DMN and TPN after
psilocybin vs placebo (figure3B, P=.001) and post- vs
prepsilocybin injection (figure3C, P=009).
Correlations Between DMN-RSN FC and Psychedelic
Effects
Pearsons correlational analyses were performed to test
for relationships between altered DMN-RSN FC and
psilocybins subjective effects. There were suggestions of
Functional Connectivity Measures
positive correlations between DMN-TPN FC and ratings
of psychedelic effects. The item my thinking was mud-
dled showed suggestions of a relationship with increased
DMN-rFPN FC, but this did not survive correction for
multiple comparison (P=.02, revised =0.002); ratings
of drug effects intensity showed suggestions of a relation-
ship with increased DMN-TPN FC, but this was also not
significant (P=.16).
DMN and TPN Connectivity With the Thalamus
Previous work found a positive correlation between
increases in DMN-TPN FC and propofol-induced reduc-
tions in consciousness23; however, none of our subjects
reported reduced consciousness after psilocybin. The
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same study also reported reduced thalamocortical con-
nectivity that correlated with reduced consciousness;
thus, we tested to see if psilocybin caused similar reduc-
tions in thalamocortical connectivity. Thalamic-DMN
FC showed a nonsignificant increase after psilocybin
(figure4D,E), and there was a significant increase in tha-
lamic-TPN FC (figure4G). The increases in thalamocor-
tical FC after psilocybin did not correlate with ratings of
the intensity of the subjective effects of psilocybin.
ValidityTests
Between-Condition Differences in Movement. Movement
regressors were included in all of our FC analyses, but
it remains possible that the increases in FC between the
aDMN and other RSNs may have been caused by differ-
ent levels of movement in the 2 conditions. Thus, we cal-
culated the mean movement per volume for each subjects
scan and compared the psilocybin and placebo scans in
a paired t test. Significantly, greater movement was seen
under psilocybin (mean movement per volume=0.06mm
[SD=0.015] for placebo vs 0.1mm [SD=0.05] for psilo-
cybin, P < .01). However, there was considerable variabil-
ity in movement under psilocybin, with some participants
showing less movement under drug. Therefore, to test
whether the between-condition differences in movement
could explain the regression results shown in figure1, we
ran correlational analyses on all of the positive results
from this analysis (ie, aDMN-DAN, aDMN-rFPN,
aDMN-SAL, and aDMN-AUD). No relationships were
found between the changes in between-network coupling
under psilocybin and the differences in movement, so the
argument that the observed changes in between-network
coupling were caused by between-condition differences in
movement is not supported by the data.
Discussion
ICA revealed 11 RSNs, including a canonical DMN.
Increased FC was evident between this DMN and 4
RSNs. These 4 RSNs include well-characterized TPNs,
ie, the dorsal attention, salience and right frontoparietal
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Fig.2. The effect of psilocybin on DMN connectivity seen at the single-subject level. (A) The aDMN (orange) and salience network
(blue) derived from Independent Components Analysis. (B) An illustrative single-subject time series for the DMN (red) and salience
network (blue) after placebo injection. (C) The same subjects time series for the DMN and salience network after psilocybin injection.
Note the increase in FC between the DMN and salience network after psilocybin vs after placebo. (D) Positive (orange) and negative
(blue) FC with the ventromedial prefrontal cortex (vmPFC) based on data from fifteen placebo condition 12-min resting-state scans. This
vmPFC-positive network is the DMN, and the vmPFC-negative network is the task-positive network. (E) The complete time series for
the DMN and task-positive network (TPN) for a single subjects psilocybin scan. Note the increase in DMN-TPN FC after psilocybin.
Subject CR rated the intensity of the effects at 9/10 and JB 10/10.

Fig.3. Increased functional FC between the default-mode- and task-positive network under psilocybin. (A) vmPFC-positive- (DMN,
orange) and vmPFC-negative regions (TPN, blue). (B) Increased FC between the DMN and TPN after psilocybin vs placebo (P=.001).
(C) Increased FC between the DMN and TPN post vs prepsilocybin (P=.009).

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Fig.4. Thalamic connectivity with the DMN and TPN. (A) The thalamic (orange) and DMN (blue) masks from which time series were
extracted. (B) Thalamic-DMN connectivity postplacebo vs postpsilocybin (P=.1). (C) Thalamic-DMN connectivity postpsilocybin vs
prepsilocybin (P=.2). (D) The thalamic (orange) and TPN (blue) networks from which time series were extracted. (E) Thalamic-TPN
connectivity postplacebo vs postpsilocybin (P=.03). (F) Thalamic-TPN connectivity post- vs prepsilocybin (P=.06).

network, and the auditory network. Importantly, DMN
and TPN activity is normally orthogonal, or even com-
petitive,17 so increased DMN-TPN FC implies that
these networks functionality became less distinct under
psilocybin. Confirmatory results were found when we
repeated the analysis with DMN and TPN masks derived
from a seed-based FC analysis; increased DMN-TPN
FC was evident after psilocybin. These results imply
that increased DMN-TPN FC, and so decreased DMN-
TPN orthogonality, is an important characteristic of the
psychedelicstate.
The question now arises, is increased DMN-TPN cou-
pling specific to the psychedelic state? Boveroux and col-
leagues found a graded decrease in DMN-TPN inverse
coupling (or increase in DMN-TPN FC) with increasing
levels of propofol-induced sedation. However, none of
our subjects reported sedation after psilocybin; in fact,
psychedelics are often described as mind expanding.
This inconsistency in phenomenology but consistency
in physiology is intriguing. Because decreased thalamo-
cortical excitation is closely linked to reduced arousal26
and large decreases in thalamocortical connectivity were
evident in the propofol study, we tested to see if the same
thalamocortical decoupling occurred under psilocybin.
We hypothesized that if thalamocortical connectivity is
preserved in the psychedelic state, then this may explain
the psychological differences between the psychedelic
and sedated state. As shown above, thalamic FC with
the DMN was preserved under psilocybin. Moreover,
while thalamic FC with a right frontoparietal network
was decreased under propofol, thalamic-TPN connec-
tivity was actually increased under psilocybin. In sum-
mary, the results of the present study strongly imply that
increased DMN-TPN FC, especially in the presence of
preserved thalamocortical FC, is not an index of reduced
consciousness but rather a change in the specific mode or
style of consciousness.
Increased DMN-TPN coupling (or decreased inverse
coupling) has been observed in patients with schizophre-
nia2730; however, it is not known how this relates to symp-
tomatology. Increased DMN-TPN coupling has been
found in people at high risk of psychosis31 and an inability

1349
R. L.Carhart-Harris etal
to distinguish between ones internal world and the exter-
nal environment, sometimes referred to as disturbed ego
boundaries, is a hallmark of early psychoses32 and the
psychedelic state.33,34 For example, one of our volunteers
reported the following after psilocybin: It was quite dif-
ficult at times to know where Iended and where Imelted into
everything around me. And the following account is from
a patient experiencing early psychotic symptoms: My per-
sonality is in danger my self is beginning to disappear.35
It is intriguing to consider whether increased DMN-
TPN FC can explain such phenomena. Disturbed ego
boundaries is a key component of spiritual-type experi-
ences.36 It is curious therefore that increased DMN-TPN
coupling has been found in experienced mediators,37
especially those practicing a form of meditation known
as nondual awareness, which specifically promotes a
unitary state of awareness in which there is no distinc-
tion between the subject and object.38 Supplementing
the mapping between DMN activity and the sense-of-
self, decreased DMN activity has also been found in
meditation37,39,40 and the psychedelic state.24 There is
increasing evidence that DMN functioning is related to
the sense-of-self15 or the ego,16 and ego dissolution
is commonly described in meditation and the psyche-
delic state. For example, one of our volunteers reported
after psilocybin: That was real ego death stuff, a total
dissolving of the ego-boundaries ... Ionly existed as a con-
cept ... as an idea.
There is a fundamental motivation towards organiza-
tion in biological systems. However, it is also know that
biological systems retain a degree of stochasticity in
their processes, so to enable flexibility. An imbalance in
the relative influence of these 2 factors may occur in the
psychedelic and early psychotic states. Characterizing the
psychedelic and early psychotic states as states of relative
disorganization yet heightened plasticity may enable us
to explain a range of phenomena. For example, focusing
on the psychedelic state, it is known that psychedelics can
promote suggestibility, spiritual and religious revelation,
and delusional thoughts; and there is also evidence that
they can be effective treatments for addiction and perhaps
other mental illnesses.2 All of these phenomena presum-
ably rely on heightened plasticity in the brain. Translating
this to psychosis lends emphasis to the importance of
early intervention because it suggests that there is a win-
dow of opportunity for changes in associative learning in
the early phase of the disorder.
To conclude, this study found increased DMN-TPN
FC using 2 complementary FC analyses. Secondary
analyses of thalamocortical FC were carried out to
explore differences between the psychedelic and sedated
state. These analyses revealed preserved thalamocortical
FC, which is opposite to the effects of sedation. We pro-
pose that increased DMN-TPN coupling in the presence
of preserved thalamocortical connectivity is related to
a state in which arousal is preserved but the distinction
1350
between inner thought and external focus becomes
blurred.
This is the first time that between-network FC has been
assessed after a psychedelic. The findings make an impor-
tant contribution to our understanding of the brain
effects of these drugs. The phenomenological and neuro-
biological association between the psychedelic state, early
psychosis and spiritual-type experiences suggest that psy-
chedelics may serve as models of the prodrome to psy-
chosis, as well as tools to deconstruct abstract concepts
such as the ego and scientifically study mystical-type
experiences.
Funding
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Beckley Foundation; Neuropsychoanalysis Foundation;
Multidisplinary Association for Psychedelic Studies; and
Heffter Research Institute.
Acknowledgments
We are grateful to the reviewers for improving this manu-
script. We are also grateful to Alison Diaper, Ann Rich,
Sue Wilson for help with this research.
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